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1.
J Pharm Biomed Anal ; 185: 113220, 2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-32145537

RESUMO

Lung cancer (Lca) is one of the malignant tumors with the fastest morbidity and mortality increase and the greatest threat to human health and life. The incidence of non-small cell lung cancer (NSCLC) in the nonsmoking female has increased recently. However, its pathogenesis is still unclear, and there is an urgent need for clinical diagnostic biomarkers, especially for early diagnosis. A nontargeted lipidomic approach based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS), as well as two machine learning approaches (genetic algorithm and binary logistic regression) was used to screen candidate discriminating lipids and define a combinational lipid biomarker in serum samples to distinguish female patients with NSCLC from healthy controls. Moreover, the candidate biomarkers were verified by using an external validation sample set. Our result revealed that fatty acid (FA) (20:4), FA (22:0) and LPE (20:4) can serve as a combinational biomarker for distinguishing female patients with NSCLC from healthy control with good sensitivity and specificity. Furthermore, this combinational biomarker also showed good performance in distinguishing early-stage NSCLC female patients from a healthy control. We observed that levels of unsaturated fatty acids clearly decreased, while saturated fatty acids and lysophosphatidylethanolamines pronouncedly increased in Lca patients, compared with the healthy controls, which revealed significant disturbance of lipid metabolism in NSCLC females. Our results not only provide hints to the pathological mechanism of NSCLC in nonsmoking female but also supply a combinational lipid biomarker to aid the diagnosis of NSCLC at early-stage.

2.
Anal Chim Acta ; 1105: 120-127, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32138910

RESUMO

Urine-based metabolomics-driven strategies for the discovery of biomarkers are increasingly developed and applied in analytical chemistry. But valid, data-based recommendations for a urine sample material of choice are lacking. We investigated first and second morning urine (MU), which are the most commonly used urine specimens. Potential major factors biasing metabolomics biomarker results in these sample materials were studied. First, 35 1st and 2nd MU samples were collected from healthy, young men after an overnight fast. Subsequently, two subgroups were built, one having fast food at lunch and dinner (n = 17), the other vegetarian meals (n = 18). Again 1st and 2nd MU were collected. Non-targeted liquid chromatography-mass spectrometry was applied for analyses. More than half of the >5400 urinary ion features showed a significant difference between 1st and 2nd MU. Just two fast food meals on previous day significantly affected around 30% of all metabolites in 1st and 2nd MU. In contrast, the effects of two vegetarian meals in 2nd MU were only minor. Additionally, we describe 47 metabolites in urine, possible hits in biomarker studies, which are susceptible to the diet the day before sample collection. They should be handled with caution until validation in diet-controlled studies. Based on our results we think the second MU, ideally collected after standardized vegetarian meals and drinking only water on the previous day, is most suitable for valid analysis of biomarkers in urine.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32101032

RESUMO

Little is known about xenometabolites in human metabolism, particularly under exercising conditions. Previously, an exercise-modifiable, likely xenometabolite derivative, cis-3,4-methylene-heptanoylcarnitine, was reported in human plasma. Here, we identified trans-3,4-methylene-heptanoylcarnitine, and its cis-isomer, in plasma and skeletal muscle by liquid chromatography-mass spectrometry. We analyzed the regulation by exercise and the arterial-to-venous differences of these cyclopropane ring-containing carnitine esters over the hepato-splanchnic bed and the exercising leg in plasma samples obtained in three separate studies from young, lean and healthy males. Compared to other medium-chain acylcarnitines, the plasma concentrations of the 3,4-methylene-heptanoylcarnitine isomers only marginally increased with exercise. Both isomers showed a >2-fold increase in the skeletal muscle tissue of the exercising leg; this may be due to the net effect of fatty acid oxidation in the exercising muscle and uptake from blood. The latter idea is supported by a >2-fold increased net uptake in the exercising leg only. Both isomers showed a constant release from the hepato-splanchnic bed, with an increased release of the trans-isomer after exercise. The isomers differ in their plasma concentration with a four times higher concentration of the cis-isomer regardless of the exercise state. This is the first approach studying kinetics and fluxes of xenolipid isomers from tissues under exercised conditions, supporting the hypothesis that hepatic metabolism of cyclopropane ring-containing fatty acids is one source of these acylcarnitines in plasma. The data also provide clear evidence for an exercise-dependent regulation of xenometabolites, opening perspectives for future studies about the physiological role of this largely unknown class of metabolites.

4.
Theranostics ; 10(5): 2029-2046, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32089734

RESUMO

Metabolic syndrome (MTS) is a cluster of concurrent metabolic abnormal conditions. MTS and its component metabolic diseases are heterogeneous and closely related, making their relationships complicated, thus hindering precision treatment. Methods: We collected seven groups of samples (group a: healthy individuals; group b: obesity; group c: MTS; group d: hyperglycemia, group e: hypertension, group f: hyperlipidemia; group g: type II diabetes, n=7 for each group). We examined the molecular characteristics of each sample by metabolomic, proteomic and peptidomic profiling analysis. The differential molecules (including metabolites, proteins and peptides) between each disease group and the healthy group were recognized by statistical analyses. Furthermore, a two-step clustering workflow which combines multi-omics and clinical information was used to redefine molecularly and clinically differential groups. Meanwhile, molecular, clinical, network and pathway based analyses were used to identify the group-specific biological features. Results: Both shared and disease-specific molecular profiles among the six types of diseases were identified. Meanwhile, the patients were stratified into three distinct groups which were different from original disease definitions but presented significant differences in glucose and lipid metabolism (Group 1: relatively favorable metabolic conditions; Group 2: severe dyslipidemia; Group 3: dysregulated insulin and glucose). Group specific biological signatures were also systematically described. The dyslipidemia group showed higher levels in multiple lipid metabolites like phosphatidylserine and phosphatidylcholine, and showed significant up-regulations in lipid and amino acid metabolism pathways. The glucose dysregulated group showed higher levels in many polypeptides from proteins contributing to immune response. The another group, with better glucose/lipid metabolism ability, showed higher levels in lipid regulating enzymes like the lecithin cholesterol acyltransferase and proteins involved in complement and coagulation cascades. Conclusions: This multi-omics based study provides a general view of the complex relationships and an alternative classification for various metabolic diseases where the cross-talk or compensatory mechanism between the immune and metabolism systems plays a critical role.

5.
J Proteome Res ; 19(1): 455-463, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31601105

RESUMO

The pituitary gland is a small but important organ located in the base of the brain. Although mostly noncancerous, pituitary adenomas (PAs) can cause serious health problems such as headaches, visual field defects, double vision, and hypopituitarism by invasion of regional structures. Nonfunctioning PAs (NFPAs) approximately account for one-third of PAs manifested by no circulating hormone hypersecretion. Lipid reprogramming has been recognized as a hallmark of tumor cells and proven to play a crucial role in tumorigenesis. However, the lipid molecular pathogenesis of NFPAs has remained obscure to date. To uncover lipid alterations that may contribute to the development of NFPAs and define their molecular characteristics, we investigated tissue lipids of patients with NFPAs including eight null cell adenomas (NCAs) and eight oncocytomas (OCMs) and of five normal pituitary glands as the control (Ctrl) using nontargeted lipidomics based on ultrahigh-performance liquid chromatography-Orbitrap Q-Exactive HF mass spectrometry. The lipidomic results were further validated in another set of subjects consisting of 8 NCAs, 10 OCMs, and 6 Ctrls to define crucial lipids discriminating NFPAs from the normal pituitary tumors. Lipidomic analyses revealed that OCM showed more pronounced changes in lipid compositions than NCA and Ctrl. As expected, mitochondria abundant cardiolipins were remarkably increased in OCM, which was accordant with the biochemical evidence of mitochondria hyperplasia in OCM. Significantly increased levels of phospholipids (PLs), especially arachidonic acid (AA)-enriched PLs, were unique characteristics of lipid profiling in OCM vs Ctrl. Our results indicate that AA-PLs may have diagnostic potential for OCM.

6.
J Sep Sci ; 43(1): 120-133, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31747121

RESUMO

Lung cancer is the leading type of cancer worldwide in terms of the number of new cases and is responsible for the largest number of deaths due to poor prognosis and difficult early detection. Due to its ability to detect numerous small molecular metabolites simultaneously, metabolomics has been widely used for the assessment of global metabolic changes in a living organism to discover candidate biomarkers for cancer diagnosis, investigate the development of cancer, and provide insights into the underlying pathophysiology. This review will mainly describe recent developments in lung cancer metabolomics in terms of early-stage detection, biomarker discovery and mechanism exploration by using nuclear magnetic resonance, liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and capillary electrophoresis-mass spectrometry in the last 10 years. The sample collection and metabolite extraction methods are also summarized.

7.
J Chromatogr A ; 1614: 460709, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31784081

RESUMO

Steroid hormones are a type of crucial substances that mediate numerous vital physiological functions. The comprehensive detection of steroid hormones can help understand the physiopathologic mechanism of steroid hormone-related diseases. It is very difficult to determine steroid hormones in biological samples due to their low endogenous concentrations and poor ionization efficiency. In this study, an efficient and sensitive approach was developed for profiling steroid hormones by combining liquid-liquid extraction and parallel derivatization with liquid chromatography-tandem mass spectrometry. Methoxyamine and dansyl chloride were used to derivatize steroid hormones containing carbonyl and phenolic hydroxyl groups, respectively. Our established method achieved simultaneous analysis of carbonyl and phenolic hydroxyl-containing steroid hormones and could cover estrogens, androgens, corticoids and progestogens. Twenty-nine steroid hormones were detected at pg/mL levels with the sensitivity enhanced by three orders of magnitude after derivatization. The linearity (with linear range of 2-4 orders of magnitude), precision (less than 15%) and recovery (71.1-128.7%) were satisfactory for quantitative analysis of steroid hormones. Finally, the established method was successfully employed to the determination of steroid hormones in serum samples of healthy males and females as well as ovarian cancer patients. The results showed that this approach was suitable and reliable for routine test of steroid hormones containing carbonyl and phenolic hydroxyl groups.

8.
Small ; 16(2): e1905233, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31814271

RESUMO

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. The prognosis of HCC remains very poor; thus, an effective treatment remains urgent. Herein, a type of nanomedicine is developed by conjugating Fe@Fe3 O4 nanoparticles with ginsenoside Rg3 (NpRg3), which achieves an excellent coupling effect. In the dimethylnitrosamine-induced HCC model, NpRg3 application significantly prolongs the survival of HCC mice. Further research indicates that NpRg3 application significantly inhibits HCC development and eliminates HCC metastasis to the lung. Notably, NpRg3 application delays HCC-induced ileocecal morphology and gut microbial alterations more than 12 weeks during HCC progression. NpRg3 administration elevates the abundance of Bacteroidetes and Verrucomicrobia, but decreases Firmicutes. Twenty-nine predicted microbial gene functions are enriched, while seven gene functions are reduced after NpRg3 administration. Moreover, the metabolomics profile presents a significant progression during HCC development, but NpRg3 administration corrects tumor-dominant metabolomics. NpRg3 administration decreases 3-indolepropionic acid and urea, but elevates free fatty acids. Importantly, NpRg3 application remodels the unbalanced correlation networks between gut microbiota and metabolism during HCC therapy. In conclusion, nanoparticle conjugation of ginsenoside Rg3 inhibits HCC development and metastasis via the remodeling of unbalanced gut microbiota and metabolism in vivo, providing an antitumor therapy strategy.

9.
Talanta ; 208: 120439, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816710

RESUMO

Marine Streptomyces is a potential source of novel bioactive natural products in medicine and agriculture. The current discrimination and screening method of Streptomyces isolates is not accurate and time-consuming, and a novel method is necessary. In this study, a protein profiling method based on an ultrahigh resolution 15 T Matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS) was established and applied for differentiation and bioactivity screening of marine Streptomyces isolates. To obtain robust protein profiling, the effects of the protein extraction method, the matrix-solvent, the sample deposition mode, and the culture time of isolates on protein profiling were thoroughly studied, the optimal conditions were obtained. To evaluate the performance of the developed MALDI-FTICR MS method, MALDI-time of flight (TOF) MS and 16S rRNA were applied in parallel to analyze 25 marine Streptomyces isolates. We found that the clustering result of MALDI-FTICR MS was more similar to that of 16S rRNA than MALDI-TOF MS. And MALDI-FTICR MS could effectively indicate the antibacterial activity of Streptomyces isolates against three plant pathogenic bacteria including Xanthomonas campestris, Xanthomonas oryzae and Erwinia carotovora. Furthermore, a differential protein/peptide was defined and successfully applied to predict antibacterial activity of blind samples. This study demonstrated that MALDI-FTICR MS has great potential to discriminate and screen complex microorganisms, especially those closely related strains.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31825515

RESUMO

CONTEXT: The liver is crucial to maintain energy homeostasis during exercise. Skeletal muscle-derived metabolites can contribute to the regulation of hepatic metabolism. OBJECTIVE: We aim to elucidate which metabolites are released from the working muscles and taken up by the liver in exercising humans and their potential influence on hepatic function. METHODS: In two separate studies, young healthy males fasted overnight and performed an acute bout of exercise. Arterial-to-venous differences of metabolites over the hepato-splanchnic bed and over the exercising and resting leg were investigated by capillary electrophoresis- and liquid chromatography-mass spectrometry metabolomics platforms. Liver transcriptome data of exercising mice were analyzed by pathway analysis to find a potential overlap between exercise-regulated metabolites and activators of hepatic transcription. RESULTS: During exercise, hepatic O2 uptake and CO2 delivery were increased two-fold. In contrast to all other free fatty acids, FFA with 18 carbon atoms and more and a high degree of saturation showed a constant release in the liver vein and only minor changes by exercise. FFA 6:0 and 8:0 were released from the working leg and taken up by the hepato-splanchnic bed. Succinate and malate showed a pronounced hepatic uptake during exercise and were also released from the exercising leg. The transcriptional response in the liver of exercising mice indicates the activation of HIF-, NRF2-, and cAMP-dependent gene transcription. These pathways can also be activated by succinate. CONCLUSION: Metabolites circulate between working muscles and the liver and may support the metabolic adaption to exercise by acting both as substrates and as signaling molecules.

11.
Lipids Health Dis ; 18(1): 179, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31639005

RESUMO

BACKGROUND: Ceramide plays pathogenic roles in nonalcoholic fatty liver disease (NAFLD) via multiple mechanisms, and as such inhibition of ceramide de novo synthesis in the liver may be of therapeutically beneficial in patients with NAFLD. In this study, we aimed to explore whether inhibition of ceramide signaling by myriocin is beneficial in animal model of NAFLD via regulating autophagy. METHODS: Sprague Dawley rats were randomly divided into three groups: standard chow (n = 10), high-fat diet (HFD) (n = 10) or HFD combined with oral administration of myriocin (0.3 mg/kg on alternate days for 8 weeks) (n = 10). Liver histology and autophagy function were measured. HepG2 cells were incubated with fatty acid with or without myriocin treatment. Lipid accumulation and autophagy markers in the HepG2 cells were analyzed. Serum ceramide changes were studied in 104 subjects consisting healthy adults, liver biopsy-proven patients with NAFLD and liver biopsy-proven patients with chronic hepatitis B (CHB). RESULTS: Myriocin reversed the elevated body weight and serum transaminases and alleviated dyslipidemia in HFD fed rats. Myriocin treatment significantly attenuated liver pathology including steatosis, lobular inflammation and ballooning. By qPCR analysis, it was revealed that myriocin corrected the expression pattern of fatty acid metabolism associated genes including Fabp1, Pparα, Cpt-1α and Acox-2. Further, myriocin also restored the impaired hepatic autophagy function in rats with HFD-induced NASH, and this has been verified in HepG2 cells. Among the sphingolipid species that we screened in lipidomic profiles, significantly increased ceramide was observed in NASH patients as compared to the controls and non-NASH patients, regardless of whether or not they have active CHB. CONCLUSIONS: Ceramide may play an important regulatory role in the autophagy function in the pathogenesis of NASH. Hence, blockade of ceramide signaling by myriocin may be of therapeutically beneficial in NASH. TRIAL REGISTRATION: Registration ID: ChiCTR-DDT-13003983 . Data of registration: 13 May, 2013, retrospectively registered.

12.
Se Pu ; 37(8): 887-896, 2019 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-31642260

RESUMO

Speckle type BTB/POZ protein (SPOP) is one of the most frequently mutated protein in prostate cancer. In this study, proteomics and metabolomics were integrated to study the effects of SPOP mutation on metabolism. First, LNCaP control (CON), SPOP wild-type (SPOP_WT), and SPOP mutation (SPOP_Y87N and SPOP_F133L) cells were subjected to a metabolomics study. The metabolomics data of LNCaP CON, SPOP_WT, SPOP_Y87N, and SPOP_F133L cells were evaluated by partial least squares-discriminant analysis (PLS-DA). Four groups could be clearly differentiated with an explanation ability of R2X=0.512, R2Y=0.616 and predictive ability of Q2=0.475. Totally, 36 differential metabolites were defined with variable importance for the projection (VIP) value > 1. Then, the 36 metabolites were subjected to one-way ANOVA analysis. Fumaric acid, malic acid, citric acid, aspartic acid, and asparagine were increased in LNCaP SPOP mutation cells compared to that in LNCaP SPOP_WT cells. Using a proteomics study, 909 differential proteins were found in LNCaP SPOP_Y87N and SPOP_F133L cells. MetaboAnalyst 3.0 was used to enrich metabolic pathways by using differential metabolites. KOBAS 3.0 was used to enrich metabolic pathways by using differential proteins. Both metabolomics and proteomics analysis showed that the tricarboxylic acid (TCA) cycle and aminoacyl-tRNA biosynthesis were significantly changed. To validate these findings, gas chromatography-mass spectrometry (GC-MS)-based metabolomics was performed in Du145 SPOP knock-out cells. The results indicated that the TCA cycle was activated in Du145 SPOP knock-out cells. Collectively, this study found that SPOP mutation significantly promoted TCA cycle in prostate cancer cells.


Assuntos
Domínio BTB-POZ , Metabolômica , Proteínas Nucleares/genética , Neoplasias da Próstata/genética , Proteômica , Proteínas Repressoras/genética , Linhagem Celular Tumoral , Ciclo do Ácido Cítrico , Humanos , Masculino , Redes e Vias Metabólicas , Mutação
13.
Anal Bioanal Chem ; 411(24): 6377-6386, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31384984

RESUMO

Omics techniques develop quickly and have made a great contribution to disease study. Omics data are usually complex. How to analyze the data and mine important information has been a key part in omics research. To study the nature of disease mechanisms systematically, we propose a new data analysis method to define the network biomarkers based on horizontal comparison (DNB-HC). DNB-HC performs molecule horizontal relationships to characterize the physiological status and differential network analysis to screen the biomarkers. We applied DNB-HC to analyze a large-scale metabolomics data, which contained 550 samples from a nested case-control hepatocellular carcinoma (HCC) study. A network biomarker was defined, and its areas under curves (AUC) in the receiver-operating characteristic (ROC) analysis for HCC discrimination were larger than those defined by six efficient feature selection methods in most cases. The effectiveness was further corroborated by another nested HCC dataset. Besides, the performance of the defined biomarkers was better than that of α-fetoprotein (AFP), a commonly used clinical biomarker for distinguishing HCC from high-risk population of liver cirrhosis in other two independent metabolomics validation sets. All and 90.3% of the AFP false-negative patients with HCC were correctly diagnosed in these two sets, respectively. The experimental results illustrate that DNB-HC can mine more important information reflecting the nature of the research problems by studying the feature horizontal relationship systematically and identifying effective disease biomarkers in clinical practice. Graphical abstract.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Metabolômica , Adulto , Estudos de Casos e Controles , Cromatografia Líquida/métodos , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos , alfa-Fetoproteínas/metabolismo
14.
Medicine (Baltimore) ; 98(31): e16717, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374067

RESUMO

This study aims to determine the non-invasive, reliable and sensitive biochemical parameters for the diagnosis of drug-induced liver injury (DILI).Ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) and selected reaction monitoring (SRM) were used to profile the serum metabolome and quantify 15 targeted bile acid metabolites, respectively, in samples obtained from 38 DILI patients and 30 healthy controls.A comparison of the resulting serum metabolome profiles of the study participants revealed significant differences between DILI patients and healthy controls. Specifically, serum palmitic acid, taurochenodeoxycholic acid, glycocholic acid (GCA), and tauroursodeoxycholic acid (TUDCA) levels were significantly higher, and serum lysophosphatidylethanolamine levels were significantly lower in DILI patients vs healthy controls (P < .001). Furthermore, the SRM assay of bile acids revealed that the increase in GCA, taurocholic acid (TCA), TUDCA, glycochenodeoxycholic acid (GCDCA), glycochenodeoxycholic sulfate (GCDCS), and taurodeoxycholic acid (TDCA) corresponded to a higher degree of liver damage. These results also indicate that serum concentrations of chenodeoxycholic acid (CDCA), deoxycholic acid (DCA) and lithocholic acid (LCA) were significantly lower in patients with severe DILI, when compared to healthy controls, and that this decrease was closely correlated to the severity of liver damage.Taken together, these results demonstrate that bile acids could serve as potential biomarkers for the early diagnosis and severity of DILI.


Assuntos
Ácidos e Sais Biliares/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Metaboloma , Biomarcadores/sangue , Estudos de Casos e Controles , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Cromatografia Líquida , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Espectrometria de Massas em Tandem
16.
J Transl Med ; 17(1): 291, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31455412

RESUMO

BACKGROUND: Pituitary adenomas are common brain tumors. Although transsphenoidal surgery are able to achieve extensive tumor removal, the rate of recurrence ranges from 5 to 20% depending on the different subtype. Further understanding of these tumors is needed to develop novel strategies to improve the prognosis of patients. But their metabolic characteristics are largely unknown. METHODS: We used metabolomic, transcriptomic, and proteomic approaches to systematically investigate eight subtypes of pituitary adenomas and normal pituitary glands. By blocking IDH2, we investigate IDH2 play an inhibitory role in GH tumor cell growth and tumor secretion. RESULTS: We found that all of the pituitary adenomas displayed downregulated glucose metabolism and glycolysis compared to normal tissues. Together with the differences in amino acids and fatty acids, we categorized these tumors into three clusters. We then re-established the reprogrammed metabolic flux in pituitary adenomas based on multiomic analyses. Take growth hormone-secreting pituitary adenomas as an example, we revealed that IDH2 is a key player in the reprogrammed metabolism of such tumors. By blocking IDH2, we confirmed that IDH2 is a potential target for the inhibition of tumor cell growth and tumor secretion. CONCLUSIONS: Our study first uncovered the metabolic landscape of pituitary adenomas and demonstrated a possible way to inhibit tumor growth by regulating aberrant metabolism.

17.
Front Chem ; 7: 468, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31334217

RESUMO

Herein, we present a systematic study on the preparation of polydopamine (PDA) hollow capsules by templating silica particles which were subsequently removed by a PDA mediated water dissolution process without using any harsh chemical treatment. It was found that the time required for silica removal varied depending on the PDA coating and dissolution conditions. Factors that could influence the core removal process including the PDA thickness and coating temperature, silica calcination duration and the availability of water were then examined in detail. Additionally, catalase was used as a model enzyme to be encapsulated into PDA hollow capsules and its bio-functionality was found to remain active. The bioactivity test results also indicated that the as-synthesized PDA capsules possessed a porous structure, which allows the penetration of small molecules such as H2O2. This study offers a better insight into silica dissolution process that mediated by PDA and contributes to the development of an eco-friendly approach for the fabrication of hollow capsules that have promising applications in drug delivery systems.

18.
Front Mol Neurosci ; 12: 159, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31316347

RESUMO

Spinocerebellar ataxia 3, also known as Machado-Joseph disease (SCA3/MJD), is a rare autosomal-dominant neurodegenerative disease caused by an abnormal expansion of CAG repeats in the ATXN3 gene. In the present study, we performed a global metabolomic analysis to identify pathogenic biochemical pathways and novel biomarkers implicated in SCA3 patients. Metabolic profiling of serum samples from 13 preclinical SCA3 patients, 13 symptomatic SCA3 patients, and 15 healthy controls were mapped using ultra-high-performance liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry techniques. The symptomatic SCA3 patients showed a metabolic profile significantly distinct from those of the preclinical SCA3 patients and healthy controls. The principal differential metabolites were involved in the amino acid (AA) metabolism and fatty acid metabolism pathways. In addition, four candidate serum biomarkers, FFA 16:1 (palmitoleic acid), FFA 18:3 (linolenic acid), L-Proline and L-Tryptophan, were selected to discriminate between symptomatic SCA3 patients and healthy controls by receiver operator curve analysis with an area under the curve of 0.979. Our study demonstrates that symptomatic SCA3 patients present distinct metabolic profiles with perturbed AA metabolism and fatty acid metabolism, and FFA 16:1, FFA 18:3, L-Proline and L-Tryptophan are identified as potential disease biomarkers.

19.
Am J Physiol Endocrinol Metab ; 317(2): E374-E387, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31211616

RESUMO

Mitochondria are dynamic organelles with diverse functions in tissues such as liver and skeletal muscle. To unravel the mitochondrial contribution to tissue-specific physiology, we performed a systematic comparison of the mitochondrial proteome and lipidome of mice and assessed the consequences hereof for respiration. Liver and skeletal muscle mitochondrial protein composition was studied by data-independent ultra-high-performance (UHP)LC-MS/MS-proteomics, and lipid profiles were compared by UHPLC-MS/MS lipidomics. Mitochondrial function was investigated by high-resolution respirometry in samples from mice and humans. Enzymes of pyruvate oxidation as well as several subunits of complex I, III, and ATP synthase were more abundant in muscle mitochondria. Muscle mitochondria were enriched in cardiolipins associated with higher oxidative phosphorylation capacity and flexibility, in particular CL(18:2)4 and 22:6-containing cardiolipins. In contrast, protein equipment of liver mitochondria indicated a shuttling of complex I substrates toward gluconeogenesis and ketogenesis and a higher preference for electron transfer via the flavoprotein quinone oxidoreductase pathway. Concordantly, muscle and liver mitochondria showed distinct respiratory substrate preferences. Muscle respired significantly more on the complex I substrates pyruvate and glutamate, whereas in liver maximal respiration was supported by complex II substrate succinate. This was a consistent finding in mouse liver and skeletal muscle mitochondria and human samples. Muscle mitochondria are tailored to produce ATP with a high capacity for complex I-linked substrates. Liver mitochondria are more connected to biosynthetic pathways, preferring fatty acids and succinate for oxidation. The physiologic diversity of mitochondria may help to understand tissue-specific disease pathologies and to develop therapies targeting mitochondrial function.


Assuntos
Metabolismo Energético/fisiologia , Fígado/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Músculo Esquelético/metabolismo , Proteoma/metabolismo , Animais , Feminino , Humanos , Fígado/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Musculares/metabolismo , Proteínas Mitocondriais/análise , Músculo Esquelético/química , Especificidade de Órgãos , Mapeamento de Peptídeos/métodos , Proteoma/análise
20.
Anal Chim Acta ; 1067: 79-87, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31047152

RESUMO

In metabolomics research, false positive features from non-sample sources and noises usually exist in the peak table, they will make the results of screening differential metabolites or biomarkers unreliable. In this study, a method to remove false positive features (rFPF) was developed to improve the quality of the peak table. rFPF recognizes real peak profiles based on the information entropy and statistical correlation, and eliminates false positive features from non-sample sources and noises. A standard mixture with 42 standards (14 isotopic labeled internal standards and 28 common standards) and a urine sample were applied to evaluate the effectiveness of the rFPF method. The analysis results of metabolite standards showed that more than 92% false positive features were removed by rFPF, but target standards completely remained. The analysis results of urine sample showed that the number of features was significantly reduced from 7182 to 2522. Interestingly, 98% of the identified metabolites remained after removing false positive features. The proposed rFPF shows great prospects as a new data handling method for metabolomics studies. The MATLAB code and data can be downloaded from http://app.ifc.dicp.ac.cn/Confirmation/Authentication.html.


Assuntos
Espectrometria de Massas , Metabolômica/métodos , Metabolômica/normas , Reações Falso-Positivas , Voluntários Saudáveis , Humanos
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